Early Conversion From CNI to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function

Status unconfirmed · Phase 2

Conditions studied: Delayed Graft Function, Kidney Transplant

In brief

The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they have developed SGF or DGF they will be randomized to convert to Belatacept or continue on their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal biopsy at Month 12 post transplant. Research Hypotheses: Primary Hypotheses: * Kidneys with slow or delayed graft function are more susceptible to acute and long-term CNI toxicity * Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have improved 1 year calculated GFR. Key Secondary Hypotheses: * Renal Histology: Belatacept converted patients will have a lower chronic allograft damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA) score as calculated by Banff criteria at 1 year post- transplant * Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections can 1) directly assess CNI induced kidney injury and 2) improve the prediction of patients that benefit in early belatacept conversion.

Key facts

Study ID: NCT01837043
Run by: Nair, Vinay, D.O.
People needed: 90
Starts: 2013-06-01
Expected to finish: 2017-06-01
Last updated by the study team: 2017-01-30

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
All patients (> 18 years) who have received a deceased donor transplant and are at risk for SGF/DGF will be studied
All gender and ethnicities will be considered in this study
At risk for SGF/DGF is defined as:
ECD (Extended Criteria Donor) donor kidney recipients
ECD is defined as a donor over the age of 60 or age 50 to 60 with 2 of the following risk factors:
Terminal creatinine > 1.5 mg/dL
History of Hypertension
Death due to cerebrovascular accident
Donations after cardiac death (DCD) kidney recipients
Donor organs with an actual cold ischemia time (CIT) > 19 hours
Recipients of donor organs with a terminal creatinine > 1.5 mg/dL
Only patients who receive Thymoglobulin induction and CNI maintenance at time of randomization will be considered for the study
Men and women, 18 to 70 years of age
Reproductive status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal.
Post-menopause is defined as:
Women who have had amenorrhea for >= 12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH)level > 35 mIU/mL
Women who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL
Women who are taking hormone replacement therapy
The following are WOCBP:
Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
Women who are practicing abstinence
Women who have a partner who is sterile (due to vasectomy)
WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized
WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug.

You may not qualify if…

Seronegative or unknown EBV (Epstein Barr Virus) serostatus (due to the risk of posttransplant lymphoproliferative disorder, PTLD) predominantly involving the central nervous system
Patients with tuberculosis who have not been treated for latent infection
Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
Rejection episode before randomization
Anatomic cause of SGF/DGF such as urinary leak, obstruction or thrombosis
Patients with a prior or concurrent non-renal solid organ transplant
Patients with living donor kidneys
Patients with pediatric kidneys (age of less than 5 years)
Dual kidney transplants (from the same donor)
Immunologically high risk patients with a positive crossmatch pre- transplantation or donor specific antibody (DSA) > 5000 MFI
ABO Incompatible transplantation
Patients with HIV
Subjects with any active infection or other contraindication that would normally exclude transplantation
Patients with a history of malignancy in the last 5 years except non- melanoma skin cancer
Baseline white blood cell count less than 2,000
Baseline hemoglobin less than 8 g/dL
Patients with prior allergic reactions to belatacept
Patients with prior allergic reactions to thymoglobulin
Sex and Reproductive status - see WOCBP information in inclusion above
Subjects currently receiving immunosuppressive agent(s) for other indications such as an autoimmune disease or subjects with comorbidities that treatment with such agents are likely during the trial.
Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
Subjects previously treated with belatacept
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

Where it is running

Mount Sinai School of Medicine Recanati/Miller Transplantation Institute — New York, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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